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  1. Article ; Online: HITTING the Diagnosis: Testing for Heparin-Induced Thrombocytopenia in Cancer Patients.

    Fenelus, Maly / Peerschke, Ellinor I B

    American journal of clinical pathology

    2018  Volume 150, Issue 2, Page(s) 116–120

    Abstract: Objectives: To evaluate the use of a pretest probability score (4Ts score) in cancer patients to guide ordering of laboratory screening tests for heparin-induced thrombocytopenia (HIT).: Methods: A retrospective chart review was conducted for ... ...

    Abstract Objectives: To evaluate the use of a pretest probability score (4Ts score) in cancer patients to guide ordering of laboratory screening tests for heparin-induced thrombocytopenia (HIT).
    Methods: A retrospective chart review was conducted for patients (n = 140) in whom laboratory testing for HIT was requested. 4Ts scores were calculated and correlated with heparin-endogenous platelet factor 4 antibody enzyme-linked immunosorbent assay (ELISA) test results.
    Results: All patients with a high pretest probability of HIT (4Ts score = 6-7) had positive ELISA results, compared to 26.1% of patients with intermediate (4Ts score = 4-5) and 4.3% of patients with low (4Ts score ≤3) pretest probability. No patients with 4Ts scores of 2 or less had positive ELISA results.
    Conclusions: HIT can be ruled out in cancer patients (negative predictive value and sensitivity = 100%) with low pretest probability, defined by 4Ts scores of 2 or less, significantly reducing the need for laboratory testing in this patient population.
    MeSH term(s) Adult ; Aged ; Anticoagulants/adverse effects ; Enzyme-Linked Immunosorbent Assay ; Female ; Heparin/adverse effects ; Humans ; Male ; Middle Aged ; Neoplasms ; Retrospective Studies ; Risk Factors ; Thrombocytopenia/chemically induced ; Thrombocytopenia/diagnosis
    Chemical Substances Anticoagulants ; Heparin (9005-49-6)
    Language English
    Publishing date 2018-06-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2944-0
    ISSN 1943-7722 ; 0002-9173
    ISSN (online) 1943-7722
    ISSN 0002-9173
    DOI 10.1093/ajcp/aqy040
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  2. Article ; Online: Complement and coagulation: key triggers of COVID-19-induced multiorgan pathology.

    Ghebrehiwet, Berhane / Peerschke, Ellinor I

    The Journal of clinical investigation

    2020  Volume 130, Issue 11, Page(s) 5674–5676

    Abstract: In a stunningly short period of time, the unexpected coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has turned the unprepared world topsy-turvy. Although the rapidity with which the ... ...

    Abstract In a stunningly short period of time, the unexpected coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has turned the unprepared world topsy-turvy. Although the rapidity with which the virus struck was indeed overwhelming, scientists throughout the world have been up to the task of deciphering the mechanisms by which SARS-CoV-2 induces the multisystem and multiorgan inflammatory responses that, collectively, contribute to the high mortality rate in affected individuals. In this issue of the JCI, Skendros and Mitsios et al. is one such team who report that the complement system plays a substantial role in creating the hyperinflammation and thrombotic microangiopathy that appear to contribute to the severity of COVID-19. In support of the hypothesis that the complement system along with neutrophils and platelets contributes to COVID-19, the authors present empirical evidence showing that treatment with the complement inhibitor compstatin Cp40 inhibited the expression of tissue factor in neutrophils. These results confirm that the complement axis plays a critical role and suggest that targeted therapy using complement inhibitors is a potential therapeutic option to treat COVID-19-induced inflammation.
    MeSH term(s) Betacoronavirus/metabolism ; Blood Platelets/metabolism ; Blood Platelets/pathology ; COVID-19 ; Complement Activation/drug effects ; Coronavirus Infections/drug therapy ; Coronavirus Infections/metabolism ; Coronavirus Infections/pathology ; Humans ; Inflammation/drug therapy ; Inflammation/metabolism ; Inflammation/pathology ; Inflammation/virology ; Neutrophils/metabolism ; Neutrophils/pathology ; Pandemics ; Peptides, Cyclic/pharmacology ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/pathology ; SARS-CoV-2 ; Severity of Illness Index ; Thromboplastin/biosynthesis ; Thrombotic Microangiopathies/drug therapy ; Thrombotic Microangiopathies/metabolism ; Thrombotic Microangiopathies/pathology ; Thrombotic Microangiopathies/virology
    Chemical Substances Peptides, Cyclic ; compstatin ; Thromboplastin (9035-58-9)
    Keywords covid19
    Language English
    Publishing date 2020-09-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI142780
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  3. Article ; Online: Classical complement pathway activation in immune thrombocytopenia purpura: inhibition by a novel C1s inhibitor.

    Peerschke, Ellinor I B / Panicker, Sandip / Bussel, James

    British journal of haematology

    2016  Volume 173, Issue 6, Page(s) 942–945

    Language English
    Publishing date 2016-06
    Publishing country England
    Document type Letter
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.13648
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  4. Article ; Online: Purification of C1q receptors and functional analysis.

    Ghebrehiwet, Berhane / Peerschke, Ellinor I B

    Methods in molecular biology (Clifton, N.J.)

    2014  Volume 1100, Page(s) 319–327

    Abstract: The recognition subunit of C1, C1q, has emerged as an important player in various pathophysiologic conditions largely in part due to its ability to interact with pathogen-associated or cell surface expressed ligands and receptors. Identification and ... ...

    Abstract The recognition subunit of C1, C1q, has emerged as an important player in various pathophysiologic conditions largely in part due to its ability to interact with pathogen-associated or cell surface expressed ligands and receptors. Identification and purification of these molecules is therefore of paramount importance if we are to procure valuable information with regards to the structure, function, and cell surface distribution. Since the interaction of C1q is better served when the receptors are purified from homologous species, we discuss here a simple guideline for the purification and characterization of the two C1q receptors, cC1qR (calreticulin) and gC1qR, from human cell lines.
    MeSH term(s) Biotinylation ; Cell Culture Techniques ; Cell Membrane/chemistry ; Cell Membrane/metabolism ; Chromatography, Liquid/methods ; Humans ; Membrane Glycoproteins/chemistry ; Membrane Glycoproteins/isolation & purification ; Membrane Glycoproteins/metabolism ; Receptors, Complement/chemistry ; Receptors, Complement/isolation & purification ; Receptors, Complement/metabolism ; U937 Cells
    Chemical Substances Membrane Glycoproteins ; Receptors, Complement ; complement 1q receptor
    Language English
    Publishing date 2014
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-62703-724-2_26
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  5. Article ; Online: C1q as an autocrine and paracrine regulator of cellular functions.

    Ghebrehiwet, Berhane / Hosszu, Kinga H / Peerschke, Ellinor I B

    Molecular immunology

    2017  Volume 84, Page(s) 26–33

    Abstract: Most of the complement proteins in circulation are, by and large, synthesized in the liver. However data accumulated over the past several decades provide incontrovertible evidence that some if not most of the individual complement proteins are also ... ...

    Abstract Most of the complement proteins in circulation are, by and large, synthesized in the liver. However data accumulated over the past several decades provide incontrovertible evidence that some if not most of the individual complement proteins are also synthesized extrahepatically by activated as well as non-activated cells. The question that is finally being addressed by various investigators is: are the locally synthesized proteins solely responsible for the myriad of biological functions in situ without the contribution of systemic complement? The answer is probably "yes". Among the proteins that are synthesized locally, C1q takes center stage for several reasons. First, it is synthesized predominantly by potent antigen presenting cells such as monocytes, macrophages and dendritic cells (DCs), which by itself is a clue that it plays an important role in antigen presentation and/or DC maturation. Second, it is transiently anchored on the cell surface via a transmembrane domain located in its A chain before it is cleaved off and released into the pericellular milieu. The membrane-associated C1q in turn, is able to sense danger patterns via its versatile antigen-capturing globular head domains. More importantly, locally synthesized C1q has been shown to induce a plethora of biological functions through the induction of immunomodulatory molecules by an autocrine- or paracrine- mediated signaling in a manner that mimics those of TNFα. These include recognition of pathogen- and danger- associated molecular patterns, phagocytosis, angiogenesis, apoptosis and induction of cytokines or chemokines that are important in modulating the inflammatory response. The functional convergence between C1q and TNFα in turn is attributed to their shared genetic ancestry. In this paper, we will infer to the aforementioned "local-synthesis-for-local function" paradigm using as an example, the role played by locally synthesized C1q in autoimmunity in general and in systemic lupus erythematosus in particular.
    MeSH term(s) Animals ; Autocrine Communication/immunology ; Complement C1q/immunology ; Dendritic Cells/immunology ; Humans ; Immune Tolerance/immunology ; Paracrine Communication/immunology
    Chemical Substances Complement C1q (80295-33-6)
    Language English
    Publishing date 2017-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 424427-8
    ISSN 1872-9142 ; 0161-5890
    ISSN (online) 1872-9142
    ISSN 0161-5890
    DOI 10.1016/j.molimm.2016.11.003
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  6. Article ; Online: Heritable platelet disorders: an enigma even guidelines can't unravel.

    Bussel, James B / Peerschke, Ellinor

    British journal of haematology

    2021  Volume 195, Issue 1, Page(s) 13–14

    Language English
    Publishing date 2021-09-07
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.17809
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  7. Article ; Online: cC1qR/CR and gC1qR/p33: observations in cancer.

    Peerschke, Ellinor I B / Ghebrehiwet, Berhane

    Molecular immunology

    2014  Volume 61, Issue 2, Page(s) 100–109

    Abstract: The survival and growth of a primary tumor depends, by and large, on three major events: immune evasion, angiogenesis and metastasis. Tumor cells are "modified self", and as such express a plethora of modified surface antigens capable of inducing ... ...

    Abstract The survival and growth of a primary tumor depends, by and large, on three major events: immune evasion, angiogenesis and metastasis. Tumor cells are "modified self", and as such express a plethora of modified surface antigens capable of inducing antibody production. Anti-tumor cell antibodies should, in theory, activate complement resulting in cell destruction. But this is not the case. Akin to many pathogenic microorganisms whose survival depends on evading the immune system, cancer cells have also evolved diverse mechanisms to prevent host mediated cell destruction by either retaining critical regulatory molecules or by hijacking host proteins to ensure their survival. Although immune evasion, angiogenesis and metastasis are complex biological processes involving a myriad of tumor associated proteins, enzymes, and cytokines, C1qRs can, nonetheless play an important role in all or part of these processes. Although both cC1qR/CR and gC1qR are expressed by all somatic cells, with the exception of red blood cells, both are highly upregulated on almost all types of tumors. It is not surprising therefore that blockade of C1qR on tumor cells inhibits their proliferation suggesting the significance of C1qRs in tumor growth and progression. Interestingly, the two C1q receptors: cC1qR/CR and gC1qR play a differential role in carcinogenesis. While gC1qR promotes tumor cell survival by enhancing angiogenesis and metastasis and also by contributing to the hypercoagulable and prothrombotic microenvironment, cC1qR/CR expression represents a pro-phagocytic "eat-me" signal through which cC1qR/CR expressing tumor cells are tagged for destruction by macrophages. The data accumulated to date therefore identify gC1qR and cC1qR/CR as potential targets for the design of either protein-based, antibody-based or chemical based therapeutic intervention that could be used to enhance conventional anti-cancer therapy. The inhibition of tumor cell proliferation by monoclonal antibody recognizing the C1q site on gC1qR, as well as the identification of agents such as anthracyclin that enhance cC1qR/CR expression on tumor cells, are indeed steps in the right direction.
    MeSH term(s) Animals ; Calreticulin/chemistry ; Calreticulin/genetics ; Calreticulin/metabolism ; Carrier Proteins/chemistry ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Complement C1q/chemistry ; Complement C1q/immunology ; Complement C1q/metabolism ; Humans ; Mitochondrial Proteins/chemistry ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/metabolism
    Chemical Substances C1QBP protein, human ; Calreticulin ; Carrier Proteins ; Mitochondrial Proteins ; Complement C1q (80295-33-6)
    Language English
    Publishing date 2014-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 424427-8
    ISSN 1872-9142 ; 0161-5890
    ISSN (online) 1872-9142
    ISSN 0161-5890
    DOI 10.1016/j.molimm.2014.06.011
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  8. Article: Is the A-Chain the Engine That Drives the Diversity of C1q Functions? Revisiting Its Unique Structure.

    Ghebrehiwet, Berhane / Kandov, Evelyn / Kishore, Uday / Peerschke, Ellinor I B

    Frontiers in immunology

    2018  Volume 9, Page(s) 162

    Abstract: ... distinct gene products: A, B, and C, each of which has evolved from a separate and unique ancestral gene ...

    Abstract The immunopathological functions associated with human C1q are still growing in terms of novelty, diversity, and pathologic relevance. It is, therefore, not surprising that C1q is being recognized as an important molecular bridge between innate and adaptive immunity. The secret of this functional diversity, in turn, resides in the elegant but complex structure of the C1q molecule, which is assembled from three distinct gene products: A, B, and C, each of which has evolved from a separate and unique ancestral gene template. The C1q molecule is made up of 6A, 6B, and 6C polypeptide chains, which are held together through strong covalent and non-covalent bonds to form the 18-chain, bouquet-of-flower-like protein that we know today. The assembled C1q protein displays at least two distinct structural and functional regions: the collagen-like region (cC1q) and the globular head region (gC1q), each being capable of driving a diverse range of ligand- or receptor-mediated biological functions. What is most intriguing, however, is the observation that most of the functions appear to be predominantly driven by the A-chain of the molecule, which begs the question: what are the evolutionary modifications or rearrangements that singularly shaped the primordial A-chain gene to become a pluripotent and versatile component of the intact C1q molecule? Here, we revisit and discuss some of the known unique structural and functional features of the A-chain, which may have contributed to its versatility.
    MeSH term(s) Adaptive Immunity ; Complement C1q/chemistry ; Complement C1q/genetics ; Complement C1q/immunology ; Complement Pathway, Classical/immunology ; Humans ; Immunoglobulin G/immunology ; Ligands ; Membrane Glycoproteins/immunology ; Peptides/chemistry ; Peptides/genetics ; Protein Structure, Tertiary ; Receptors, Complement/immunology
    Chemical Substances Immunoglobulin G ; Ligands ; Membrane Glycoproteins ; Peptides ; Receptors, Complement ; complement 1q receptor ; Complement C1q (80295-33-6)
    Language English
    Publishing date 2018-02-05
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.00162
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  9. Article ; Online: Choosing wisely during the COVID-19 pandemic: optimising outpatient cancer care while conserving resources with a new algorithm to report automated ANC results.

    Fenelus, Maly / Graham, Tamiqua / Golden, Ryan / Bautista, Jessica L / So, Rachel J / Plante, Nora / Peerschke, Ellinor I B

    Journal of clinical pathology

    2020  Volume 74, Issue 3, Page(s) 202–204

    MeSH term(s) Algorithms ; Ambulatory Care/methods ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Biomarkers/blood ; COVID-19/epidemiology ; COVID-19/therapy ; Humans ; Neoplasms/drug therapy ; Neutropenia/chemically induced ; Neutropenia/diagnosis ; Neutropenia/metabolism ; Neutrophils/metabolism ; New York City/epidemiology ; Pandemics ; Resource Allocation/methods ; Retrospective Studies
    Chemical Substances Antineoplastic Agents ; Biomarkers
    Keywords covid19
    Language English
    Publishing date 2020-11-16
    Publishing country England
    Document type Letter
    ZDB-ID 80261-x
    ISSN 1472-4146 ; 0021-9746
    ISSN (online) 1472-4146
    ISSN 0021-9746
    DOI 10.1136/jclinpath-2020-207114
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  10. Article ; Online: Analytical Validation and Performance Characteristics of Molecular Serum Biomarkers, miR-371a-3p and miR-372-3p, for Male Germ Cell Tumors, in a Clinical Laboratory Setting.

    Ye, Fei / Feldman, Darren R / Valentino, Alisa / So, Rachel / Bromberg, Maria / Khan, Shah / Funt, Samuel A / Sheinfeld, Joel / Solit, David B / Pessin, Melissa S / Peerschke, Ellinor I

    The Journal of molecular diagnostics : JMD

    2022  Volume 24, Issue 8, Page(s) 867–877

    Abstract: Detection of serum embryonic miRNAs miR-371a-3p and miR-372-3p has been proposed to aid in diagnosis, prognosis, and management of patients with testicular germ cell tumors (GCTs). This study describes the analytical validation and performance of a ... ...

    Abstract Detection of serum embryonic miRNAs miR-371a-3p and miR-372-3p has been proposed to aid in diagnosis, prognosis, and management of patients with testicular germ cell tumors (GCTs). This study describes the analytical validation and performance of a laboratory-developed test to detect these miRNA targets by stem loop real-time quantitative RT-PCR (RT-qPCR) in serum from patients with GCTs. The assay was standardized using an exogenous spike-in control of nonhuman miRNA from Caenorhabditis elegans (cel-miR-39-3p) to assess extraction efficiency, and an endogenous housekeeping miRNA, miR-30b-5p, to control for miRNA normalization. miRNA results were expressed as relative expression level, using the comparative threshold cycle method (2
    MeSH term(s) Biomarkers, Tumor/genetics ; Humans ; Laboratories, Clinical ; Male ; MicroRNAs ; Neoplasms, Germ Cell and Embryonal/diagnosis ; Neoplasms, Germ Cell and Embryonal/genetics ; Testicular Neoplasms
    Chemical Substances Biomarkers, Tumor ; MIRN372 microRNA, human ; MicroRNAs
    Language English
    Publishing date 2022-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2000060-1
    ISSN 1943-7811 ; 1525-1578
    ISSN (online) 1943-7811
    ISSN 1525-1578
    DOI 10.1016/j.jmoldx.2022.04.007
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